Maintenance of normal arterial blood gas and acid-base status in response to changes of activity level requires rapid and precise coupling of ventilation to the gas exchange demands of both altered pulmonary blood flow and mixed venous gas concentrations. However, the mechanisms which control the exercise hyperpnea remain obscure. The widely-held neurogenic theory of the exercise hyperpnea proposes that the initial ventilatory response reflects afferent neural drive which is coupled to locomotion. This theory, however, does not address the precision with which arterial blood gas tensions and pH are normally maintained through this phase of exercise. To determine the regions of important afferent drive and their relative importance, we plan to use techniques to functionally isolate the cervico-cranial, thoracic and peripheral (i.e., muscular) regions during electrically-induced, hindlimb exercise in the anesthetized dog. This model has been chosen expressly because, when intact, its hyperpneic responses to the electrically-induced exercise mimic so well those typical of the awake human, both with respect to their dynamic characteristics and to the subsequent isocapnic steady-state. The logic of our experimental design is functionally to isolate the flow and humoral consequences of exercise either to one or more of these 'regions', or away from them. Thus, we shall utilize: exercise, increased and decreased pulmonary blood flow and mixed venous C02 content, and isoproterenol or vasopression injections before and after spinal-cord section to interrupt somatic afferents from the exercising hindlimbs. In addition, we shall extend our observations to unanesthetized calves with a pneumatically-powered, chronically-implanted total artificial heart preparation which will allow independent manipulation of cardiac output and the exercise stress. Thus, we shall impose acute alterations of cardiac output both at rest and while the calves are walking on a treadmill, by a device that controls the pumping rate of the artificial heart. Ventilation and pulmonary gas exchange will be determined breath-by-breath via online digital computation, together with measurements of cardiac output and vascular pressures; and the dynamic response patterns analyzed along with the consequent blood gas changes. These will be incorporated into a control scheme which characterizes the role of cardiovascular mechanisms in the exercise hyperpnea and arterial blood gas and acid-base homeostatis.